Dolutegravir + Rilpivirine Switch Study (DORISS)
- Conditions
- HIV InfectionHAART-treatedVirologically Controlled
- Interventions
- Drug: Arm 1 (intervention)Drug: Arm 2 (control)
- Registration Number
- NCT02069834
- Lead Sponsor
- Nantes University Hospital
- Brief Summary
The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent).
The main secondary objectives are the following:
* % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48
* % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48
* % of virological failure defined by two consecutive plasma viral load \> 50 copies/mL
* Profile of genotypic resistance in case of virological failure.
The trial will be conducted according to the design below, in 3 steps:
* Step 1: enrollment of 80 patients (40 in each arm)
* Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed.
* Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly \> 70%, which translates in a maximum of 6 virologic failures.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Age ≥ 18 years
- HIV-1 infection
- Treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, or 1 NNRTI, or INI), unchanged for > 6 months, Intra-class substitution within past 6 months is not considered as a treatment change.
- Plasma HIV-RNA ≤ 50 copies/mL for > 2 years
- CD4 cell count > 350/mm3 for > 6 months
- No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen
- No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D.
- No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S
- Negative HBs Ag
- Informed consent form signed by patient and investigator
- A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study
- Patient covered with health insurance
- Effective contraception
- HIV-2 infection
- Dialysis or severe renal failure (creatinine clearance < 30 ml/min)
- History of decompensated liver disease
- History of HIV-associated neurocognitive disorders
- AST or ALT > 5 x ULN
- Positive HBc Ac and negative HBs Ac
- Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug
- Current pregnancy or breastfeeding
- Patient involved in another research that precludes enrolment in another trial
- Patient under guardianship, or deprived of liberty by a court or administrative decision.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 (intervention) Arm 1 (intervention) Dolutegravir 50 mg/d + Rilpivirine 25 mg/d qd orally (intake during a meal) Arm 2 (control) Arm 2 (control) Continuation of existing HAART at the time of randomization
- Primary Outcome Measures
Name Time Method Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16) Week 16 Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks Week 24
- Secondary Outcome Measures
Name Time Method Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48 Week 48 Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48 Week 48 Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL Week 24 Measure of the profile of genotypic resistance in plasma in case of virologic failure Week 24 Percentage of patients who discontinued or changed the strategy of the study Week 48 Measure of the HIV-DNA between day 0 and week 48 W48 Evolution of the HIV-DNA between Day 0 and week 48
Measure of CD4 lymphocytes at week 24 compared to day 0 Week 24 Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0
Measure of CD4 lymphocytes at Week 48 compared to Day 0 Week 48 Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0
Number of patients with adverse events of grade 2 to 4 Week 48 Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events
Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0 Week 24 Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0
Measure of changes in serum lipid parameters at week 48 to Day 0 Week 48 Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0
Measure of changes in fat mass distribution at week 24 compared to Day 0 Week 24 Changes in fat mass distribution at Week 24 compared to Day 0
Measure of changes in fat mass distribution at Week 48 compared to Day 0 Week 48 Changes in fat mass distribution at Week 48 compared to Day 0
Measure of adherence to treatment at Week 24 compared to Day 0 Week 24 Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire
Measure of adherence to treatment at Week 48 compared to Day 0 Week 48 Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire
Measure of patient satisfaction for their treatment at Day 0 Day 0 Assessment of patient satisfaction for their treatment at D0 by questionnaire
Measure of patient satisfaction for their treatment at Week 24 Week 24 Assessment of patient satisfaction for their treatment at Week 24 by questionnaire
Measure of patient satisfaction for their treatment at Week 48 Week 48 Assessment of patient satisfaction for their treatment at Week 48 by questionnaire
Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 . Week 24 Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 . Week 48 Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4 Week 4 Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24 Week 24 Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
Trial Locations
- Locations (25)
CHU Guadeloupe
🇫🇷Point-a-pitre, Guadeloupe, France
Chu Jean Minjoz
🇫🇷Besançon, France
Hôpital Avicenne
🇫🇷Bobigny, France
Hôpital Jean Verdier
🇫🇷Bondy, France
CHU de Nancy
🇫🇷VANDOEUVRE LES NANCY cedex, France
CHU de Strasbourg
🇫🇷Strasbourg, France
CHU de Fort de France
🇫🇷Fort de France, Martinique, France
CHD La Roche sur Yon
🇫🇷La Roche sur Yon, France
CHU de Nantes
🇫🇷Nantes, France
Hôpital Saint Louis
🇫🇷Paris Cedex 10, France
CH Delafontaine
🇫🇷Saint Denis, France
CHU de Rennes - Hôpital Pontchaillou
🇫🇷Rennes, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
CHU Saint Etienne
🇫🇷Saint Etienne, France
CHRU de Tours
🇫🇷Tours Cedex 09, France
CHU Toulouse
🇫🇷Toulouse, France
CHU de DIJON
🇫🇷Dijon, France
CHU Kremlin Bicêtre
🇫🇷Le Kremlin Bicetre, France
CHU de Bordeaux
🇫🇷Bordeaux, France
CHU BICHAT - Claude Bernard
🇫🇷Paris cedex 18, France
Hôpital Perpetuel Secours
🇫🇷Levallois-perret, France
CHU Hôtel Dieu Paris
🇫🇷Paris, France
Hôpital La Pitié Salpêtrière
🇫🇷Paris, France
Hôpital Necker - enfants Malades
🇫🇷Paris, France
Hôpital FOCH
🇫🇷Suresnes, France